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Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli

The consistently mutating bacterial genotypes appear to have accelerated the global challenge with antimicrobial resistance (AMR); it is therefore timely to investigate certain less-explored fields of targeting AMR mechanisms in bacterial pathogens. One of such areas is beta-lactamase (BLA) inductio...

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Autores principales: Mallik, Dhriti, Jain, Diamond, Bhakta, Sanjib, Ghosh, Anindya Sundar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772759/
https://www.ncbi.nlm.nih.gov/pubmed/35052944
http://dx.doi.org/10.3390/antibiotics11010067
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author Mallik, Dhriti
Jain, Diamond
Bhakta, Sanjib
Ghosh, Anindya Sundar
author_facet Mallik, Dhriti
Jain, Diamond
Bhakta, Sanjib
Ghosh, Anindya Sundar
author_sort Mallik, Dhriti
collection PubMed
description The consistently mutating bacterial genotypes appear to have accelerated the global challenge with antimicrobial resistance (AMR); it is therefore timely to investigate certain less-explored fields of targeting AMR mechanisms in bacterial pathogens. One of such areas is beta-lactamase (BLA) induction that can provide us with a collection of prospective therapeutic targets. The key genes (ampD, ampE and ampG) to which the AmpC induction mechanism is linked are also involved in regulating the production of fragmented muropeptides generated during cell-wall peptidoglycan recycling. Although the involvement of these genes in inducing class C BLAs is apparent, their effect on serine beta-lactamase (serine-BLA) induction is little known. Here, by using ∆ampD and ∆ampE mutants of E. coli, we attempted to elucidate the effects of ampD and ampE on the expression of serine-BLAs originating from Enterobacteriaceae, viz., CTX-M-15, TEM-1 and OXA-2. Results show that cefotaxime is the preferred inducer for CTX-M-15 and amoxicillin for TEM-1, whereas oxacillin for OXA-2. Surprisingly, exogenous BLA expressions are elevated in ∆ampD and ∆ampE mutants but do not always alter their beta-lactam susceptibility. Moreover, the beta-lactam resistance is increased upon in trans expression of ampD, whereas the same is decreased upon ampE expression, indicating a differential effect of ampD and ampE overexpression. In a nutshell, depending on the BLA, AmpD amidase moderately facilitates a varying level of serine-BLA expression whereas AmpE transporter acts likely as a negative regulator of serine-BLA.
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spelling pubmed-87727592022-01-21 Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli Mallik, Dhriti Jain, Diamond Bhakta, Sanjib Ghosh, Anindya Sundar Antibiotics (Basel) Article The consistently mutating bacterial genotypes appear to have accelerated the global challenge with antimicrobial resistance (AMR); it is therefore timely to investigate certain less-explored fields of targeting AMR mechanisms in bacterial pathogens. One of such areas is beta-lactamase (BLA) induction that can provide us with a collection of prospective therapeutic targets. The key genes (ampD, ampE and ampG) to which the AmpC induction mechanism is linked are also involved in regulating the production of fragmented muropeptides generated during cell-wall peptidoglycan recycling. Although the involvement of these genes in inducing class C BLAs is apparent, their effect on serine beta-lactamase (serine-BLA) induction is little known. Here, by using ∆ampD and ∆ampE mutants of E. coli, we attempted to elucidate the effects of ampD and ampE on the expression of serine-BLAs originating from Enterobacteriaceae, viz., CTX-M-15, TEM-1 and OXA-2. Results show that cefotaxime is the preferred inducer for CTX-M-15 and amoxicillin for TEM-1, whereas oxacillin for OXA-2. Surprisingly, exogenous BLA expressions are elevated in ∆ampD and ∆ampE mutants but do not always alter their beta-lactam susceptibility. Moreover, the beta-lactam resistance is increased upon in trans expression of ampD, whereas the same is decreased upon ampE expression, indicating a differential effect of ampD and ampE overexpression. In a nutshell, depending on the BLA, AmpD amidase moderately facilitates a varying level of serine-BLA expression whereas AmpE transporter acts likely as a negative regulator of serine-BLA. MDPI 2022-01-06 /pmc/articles/PMC8772759/ /pubmed/35052944 http://dx.doi.org/10.3390/antibiotics11010067 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mallik, Dhriti
Jain, Diamond
Bhakta, Sanjib
Ghosh, Anindya Sundar
Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli
title Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli
title_full Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli
title_fullStr Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli
title_full_unstemmed Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli
title_short Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli
title_sort role of ampc-inducing genes in modulating other serine beta-lactamases in escherichia coli
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772759/
https://www.ncbi.nlm.nih.gov/pubmed/35052944
http://dx.doi.org/10.3390/antibiotics11010067
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